The behavioral, biochemical, and histological effects of tissue implants in rodent and primate models of Parkinsonism is being studied. The grafts which have been-examined include fetal and adult dopaminergic and nondopaminergic tissues. There is some behavioral improvement with any operative trauma to the caudate, whether or not a graft is placed. Generally, fetal tissue grafts (dopaminergic or nondopaminergic) lead to a much greater degree of recovery than adult tissue grafts or trauma alone. The histologic observation of dopaminergic fiber ingrowth (sprouting) in all these animals suggests that the improvement is mediated through a neurotrophic interaction, We are trying to determine the cellto-cell interaction which leads to new growth of fibers from an adult neuron, using in vivo and in vitro methods. Two major areas of emphasis are: what cascade of events in the host after trauma leads to sprouting and why does fetal tissue enhance the recovery (even nondopaminergic tissue)? The experiments included implantation of fetal and term amnion into hemiparkinsonian monkeys (solid tissue into preformed cavities), cell suspension implants of term amnion into rats, IL-1 slow-release polymers implants in hemiparkinsonian rats and monkeys. To further investigate the host response to tissue implantation, we are now using direct intrastriatal infusion of chemicals known to be released by inflammatory cells. Direct infusion of trophic factors that stimulate dopaminergic growth is also being studied.